This is a Phase 1, open-label study to evaluate the drug-drug interaction potential of a strong CYP3A4 inhibitor (itraconazole) and a pan-CYP inducer (rifampin) on APX001 in two parallel groups of healthy subjects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Cohort 1 Day 1: APX001 500 mg IV BID over a 3-hour infusion; Day 18: APX001 500 mg IV BID over a 3-hour infusion. Cohort 2 Day 1: APX001 1000 mg IV BID over a 3-hour infusion; Day 24: APX001 1000 mg IV BID over a 3-hour infusion.
Cohort 1 Days 15-30: itraconazole 200 mg oral solution QD.
Cohort 2 Days 15-33: rifampin 600 mg oral QD.
PRA Health Sciences (PRA) - Early Development Services (EDS)
Groningen, Netherlands
PRA-EDS
Groningen, Netherlands
Pharmacokinetics of APX001/APX001A as measured by area under the plasma concentration-time curve (AUC) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by maximum observed plasma concentration (Cmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by time to attain maximum observed plasma concentration (Tmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by terminal elimination rate constant (λz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by terminal elimination half-life (t1/2) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by total clearance (CL) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
Pharmacokinetics of APX001/APX001A as measured by the volume of distribution during the terminal phase (Vz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin.
Time frame: 6 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Number of subjects experiencing and frequency of occurrence of adverse events as rated by CTCAE v5.0 after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Time frame: 6 weeks
Occurrence and magnitude of clinical lab test values outside the normal range, clinically significant, and differing from baseline results after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
The following parameters will be measured: * Clinical chemistry (serum quantitatively): total bilirubin, direct (conjugated) bilirubin, indirect (unconjugated) bilirubin (calculated), alkaline phosphatase, gamma-GT, ASAT, ALAT, LDH, p-amylase, lipase, CPK, creatinine, eGRF, urea, uric acid, cholesterol, triglycerides, total protein, albumin, globulin, glucose, inorganic phosphate, sodium, potassium, calcium, chloride, and bicarbonate. * Hematology (blood quantitatively): leukocytes, erythrocytes, hemoglobin, hematocrit, thrombocytes, partial automated absolute differentiation: lymphocytes, monocytes, eosinophils, basophils, neutrophils, MCV, MCH, and MCHC. * Coagulation (blood quantitatively): PT, aPTT, and fibrinogen. * Urinalysis (urine qualitatively): color, protein, glucose, bilirubin, urobilinogen, ketones, blood, pH, specific gravity, and leukocytes.
Time frame: 6 weeks
Occurrence of abnormal vital signs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Systolic and diastolic blood pressure and pulse will be recorded after the subject has been resting supine or semi-recumbent for at least 5 minutes. Body temperature and respiratory rate will be measured subsequently.
Time frame: 6 weeks
Occurrence of abnormal, clinically significant results from 12-lead ECGs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
The following ECG parameters will be recorded: heart rate, PR interval, QRS duration, QT interval, and QTc interval (Fridericia's).
Time frame: 6 weeks
Occurrence of changes in physical examinations which differ from baseline after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin.
Physical examination will include: general appearance; skin/subcutaneous tissue; head; ears, nose, throat; neck and thyroid; thorax; lungs; cardiovascular; lymph nodes; abdomen; musculoskeletal; and neurological.
Time frame: 6 weeks